Core D is subdivided in two parts: Imaging (part 1), under the responsibility of Dr. Nahrendorf, and Confocal and Two-Photon Microscopy (part 2) under the responsibility of Dr. Kajstura. Part 1 will provide sophisticated non-invasive, diagnostic imaging by MRI and other instrumentations to characterize the cardiac phenotype of aging mice and the effects of cardiac stem cells (CSCs) on the reversal of the aging process. These determinations are required for Projects 1, 2, and 4. By this approach, the anatomical and functional characteristics of myocardial aging will be followed over time in the same animals to validate targets and linked biomarkers, and assess the efficacy of emerging therapeutics. Part 2 will support all 4 Projects since they require complex immunolabeling methodologies and the necessity to distinguish actual signals from tissue autofluorescence by confocal microscopy. Additionally, the evaluation whether sarcomere stretching alone or mechanical deformation of resident CSCs promotes Ca2+ oscillatory events and cell cycle reentry will need two-photon microscopy. This strategy is particularly relevant to Projects 3 and 4. Collectively, part 1 and part 2 of Core D will ensure an unmatched level of technology and expertise, essential to achieve the goals of this PPG application. Importantly, Dr. Nahrendorf and Dr. Kajstura have been working closely together in the acquisition of the Preliminary Data included in the proposal.